Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

Purpose To investigate the clinicopathological characteristics of the gastric oxyntic gland adenoma(GOGA).Methods We collected 18 samples of GOGA,histopathological features and immunohistochemical staining were assessed.Main features of pathological diagnosis,treatment methods and follow-up were retrospectively analyzed.Results There were 18 patients,including 9 females and 9 males,aged from 36 to 86 years old.The endoscopic im-age showed a flat lesion with whitish in color or a polypoid protrusions.The size ranged from 0.3 cm to 0.8 cm.Hema-toxylin and eosin staining showed irregular glandular structures in the mucosal lamina propria,with branched and anas-tomosed patterns.The tumour demonstrating composed of chief cells hyperplasia with mild nuclear atypia.All lesions were confined to the mucous lamina propria.There was no atrophic within the peripheral gastic mucosa.Immunohisto-chemical examination showed positive for Pepsinogen-Ⅰ and MUC6.Gene mutation were analyzed in 2 cases using next generation sequence technology,and no KRAS and GNAS mutation had been detected.Endoscopic surgical treatment was performed in 11 cases,and biopsy forceps removal was carried out in 7 cases.No recurrence or metastasis was ob-served during the follow-up period of 1 to 58 months.Conclusion GOGA is a rare lesion,and appears to behave bio-logically benign.A full understanding of its histological morphology and biological behavior can improve the diagnostic ability of clinincans,and facilitate further research in the future.

Objective:To analyze the etiological characteristics of Clostridium ramosum DZS3717106 isolated from the blood of a patient with septic shock secondary to perianal abscess and the immunological characteristics of the patient. Methods:The isolate was subjected to morphological observation, mass spectrometry, antibiotic susceptibility testing, and 16S rRNA sequencing. Biochemical and cytological test results of the patient were collected. Flow cytometry was used to detect T cell subsets. Impacts of the virulence factors of the isolate on the host immune system were evaluated.Results:DZS3717106 was an anaerobic Clostridium with pleomorphic rod-shaped cells and spores. It was sensitive to penicillin G, piperacillin/tazobactam, and metronidazole, but resistant to clindamycin. It carried various virulence and resistance genes. The patient was immunocompromised with abnormal IL-6, IL-8, and IL-10 levels. Conclusions:Septic shock caused by Clostridium ramosum is rare, and more research is needed on the causes and epidemiology. DZS3717106 infection triggers over-activated inflammatory response in the patient, which may be closely related to the occurrence and development of septic shock.

Objective To investigate the occurrence risk for common complications of internal jugular vein(IJV)and subclavian vein(SCV)catheterization,and provide reference for the prevention and treatment of common com-plications during clinical intravenous infusion therapy.Methods Data from China National Knowledge Infrastruc-ture(CNKI),Wanfang Database,VIP Database,Embase(via OVID),PubMed,Cochrane Library,CINAHL,Web of Science,and ScienceDirect were retrieved,with the search period from database establishment to August 3,2023.Prospective cohort and experimental studies on common complications in patients with IJV and SCV cathete-rization were collected.Meta-analysis on the extracted data was performed with RevMan 5.3 software.Results A total of 29 studies involving 14 096 patients were included in the analysis,including 6 355 patients with SCV cathe-terization(SCV group)and 7 741 patients with IJV catheterization(IJV group).Meta-analysis results showed that the occurrence risk for hemopneumothorax(OR=0.23,95％CI[0.14-0.37])and catheter tip ectopic(OR=0.16,95％CI[0.03-0.85])in SCV group was higher than that in IJV group,and the occurrence risk for central venous catheter-related deep venous thrombosis in IJV group was higher than that in SCV group(OR=2.35,95％CI[1.31-4.21]),with statistically significant differences(all P＜0.01).There were no statistical differences in the occurrence risk of vascular catheter-related bloodstream infection(CRBSI),catheter blockage,and catheter local he-matoma between the two groups(all P＞0.05),there was difference in the combined result of subgroup analysis re-garding catheter bacterial colonization.Conclusion Compared with IJV,patients in SCV group have a higher risk of developing hemopneumothorax and catheter tip ectopic,while patients with catheterization in IJV group have a high-er risk of deep veinous thrombosis.There are no significant differences in the occurrence risk for CRBSI,catheter blockage,and catheter local hematoma between two groups of patients.It is suggested that patient's own conditions and the accessibility of deep vein catheterization should be considered more when selecting the site of deep venous catheterization.

ObjectiveTo establish a method for the identification of Haliotidis Concha and its counterfeits， and to improve its quality evaluation method. MethodsA total of 17 batches of Haliotis discus hannai， 4 batches of H. ruber， 3 batches of H. laevigata， 3 batches of H. ovina， 3 batches of H. diversicolor， 3 batches of H. asinina， 3 batches of H. iris were collected. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS/MS） was used to analyze the hydrolysates of different original Haliotidis Concha and its counterfeits， and the potential characteristic ions of each species were screened by Venn diagram. UPLC-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS） was used to validate the characteristic ions， and the specific detection method of the characteristic ions was established. ResultsA total of 1 182， 167， 47， 89， 104， 203， 424 potential characteristic ions were screened from H. discus hannai， H. ruber， H. laevigata， H. ovina， H. diversicolor， H. asinina and H. iris， respectively. And 9 characteristic ions were selected. The precision， stability and repeatability of the 9 characteristic ions in the established identification method met the requirements. Different original Haliotidis Concha and its counterfeits could detect their own characteristic ions， including m/z 631.83-886.48（double charge） and m/z 631.83-443.74（double charge） of H. discus hannai， m/z 699.28-232.11（double charge） and m/z 699.28-544.27（double charge） of H. ruber， m/z 535.76-752.37（double charge） and m/z 535.76-548.28（double charge） of H. laevigata， m/z 708.35-442.28（double charge） and m/z 708.35-215.14（double charge） of H. ovina， m/z 561.33-614.86（triple charge）， m/z 561.33-468.28（triple charge）， m/z 608.29-618.32（double charge） and m/z 608.29-390.21（double charge） of H. diversicolor， m/z 769.85-274.10（double charge）， m/z 769.85-532.75（double charge）， m/z 827.43-646.36（single charge）， m/z 827.43-257.12（single charge） of H. asinina， and m/z 468.24-576.29（double charge） and m/z 468.24-505.26（double charge） of H. iris. ConclusionIn this study， a total of 9 characteristic ions are screened from 6 kinds of original Haliotidis Concha and its counterfeits， and a specific identification method is established， which is helpful to solve the limitations of the existing quality evaluation methods of Haliotidis Concha， and provide a basis for the production， circulation and medication quality.

ObjectiveTo establish a method for the identification of Haliotidis Concha and its counterfeits， and to improve its quality evaluation method. MethodsA total of 17 batches of Haliotis discus hannai， 4 batches of H. ruber， 3 batches of H. laevigata， 3 batches of H. ovina， 3 batches of H. diversicolor， 3 batches of H. asinina， 3 batches of H. iris were collected. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS/MS） was used to analyze the hydrolysates of different original Haliotidis Concha and its counterfeits， and the potential characteristic ions of each species were screened by Venn diagram. UPLC-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS） was used to validate the characteristic ions， and the specific detection method of the characteristic ions was established. ResultsA total of 1 182， 167， 47， 89， 104， 203， 424 potential characteristic ions were screened from H. discus hannai， H. ruber， H. laevigata， H. ovina， H. diversicolor， H. asinina and H. iris， respectively. And 9 characteristic ions were selected. The precision， stability and repeatability of the 9 characteristic ions in the established identification method met the requirements. Different original Haliotidis Concha and its counterfeits could detect their own characteristic ions， including m/z 631.83-886.48（double charge） and m/z 631.83-443.74（double charge） of H. discus hannai， m/z 699.28-232.11（double charge） and m/z 699.28-544.27（double charge） of H. ruber， m/z 535.76-752.37（double charge） and m/z 535.76-548.28（double charge） of H. laevigata， m/z 708.35-442.28（double charge） and m/z 708.35-215.14（double charge） of H. ovina， m/z 561.33-614.86（triple charge）， m/z 561.33-468.28（triple charge）， m/z 608.29-618.32（double charge） and m/z 608.29-390.21（double charge） of H. diversicolor， m/z 769.85-274.10（double charge）， m/z 769.85-532.75（double charge）， m/z 827.43-646.36（single charge）， m/z 827.43-257.12（single charge） of H. asinina， and m/z 468.24-576.29（double charge） and m/z 468.24-505.26（double charge） of H. iris. ConclusionIn this study， a total of 9 characteristic ions are screened from 6 kinds of original Haliotidis Concha and its counterfeits， and a specific identification method is established， which is helpful to solve the limitations of the existing quality evaluation methods of Haliotidis Concha， and provide a basis for the production， circulation and medication quality.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

This article reported a case of a newborn with congenital absence of the penis. The prenatal examinations were unremarkable. Physical examination of the newborn revealed abnormal external genitalia, with well-developed scrotum and fully descended testicle in normal size, but without the penis. Postnatal ultrasound showed no obvious signals of uterus and ovaries in pelvis and had normal bilateral testicles and urinary system. The diagnosis was congenital absence of the penis.

Objective This study mainly focuses on the relationship between the serum glycoprotein non-metastatic melanoma protein B(GPNMB)concentration and the degree of neurological damage and prognosis in patients with acute ischemic stroke(AIS),and screens potential biomarkers to provide a reference for clinical diagnosis and treatment.Methods A total of 105 AIS patients hospitalized in the Department of Neurology of the Hospital 2 of Nantong University from June 2023 to March 2024 were selected as the sample group.In this study,the patients were divided into mild group(n=42)and moderate to severe group(n=63)according to the National Institutes of Health Strobe Scale(NIHSS)score within 24 hours of admission.The Modified Rankin Scale(mRS)was used to evaluate the functional recovery 3 months after discharge.The samples were subdivided into good prognosis group(n=34)and poor prognosis group(n=71).The serum GPNMB protein level was detected by ELISA,and the correlation between serum GPNMB protein level and NIHSS and mRS scores was analyzed.The binary Logistic regression model was used to evaluate the predictive value and prognostic evaluation value of serum GPNMB protein level for AIS neurological function damage.Results The serum GPNMB protein concentration in patients with moderate to severe neurological impairment and poor prognosis was significantly lower than that in patients with mild and good prognosis(P<0.05).The serum GPNMB protein level was significantly negatively correlated with the NIHSS score(r=-0.196,P<0.05)and the mRS score(r=-0.334,P<0.05).Multivariate regression analysis showed that GPNMB was still a key independent risk factor for AIS(P<0.05).The evaluation results obtained based on the receiver operating characteristic curve(ROC)showed that the serum GPNMB protein level had diagnostic value in predicting neurological impairment and poor prognosis(sensitivity reached 55.6%,specificity was 81.8%,and the overall accuracy was 63.81%,P<0.05).Conclusion There is a significant positive correlation between the decrease in serum GPNMB protein concentration and the degree of neurological damage in AIS patients,and it is likely to become an important biological indicator for measuring the severity of the disease and long-term prognosis.